This is a competing renewal application seeking two years of additional funding to complete the ongoing multi-site study, "Continuation ECT: Efficacy and Safety." The goal of this research is to compare continuation ECT with an aggressive combination pharmacotherapy strategy (nortriptyline plus lithium) in the prevention of depressive relapse after successful ECT for major depression. As of May 30, 2001, we have successfully enrolled 470 patients into the acute ECT phase of the study (Phase I) and 159 patients into the two treatment arm randomized phase (Phase II). This represents 73 percent of the necessary recruitment target. An additional 56 randomized patients will be enrolled to meet the target randomized sample size of 216. Completion of patient recruitment, follow-up, and analysis of results can be accomplished with the additional 24 months requested in this application. Electroconvulsive therapy (ECT) is a highly effective treatment for major depressive disorder (MDD). Relapse after acute phase ECT or pharmacotherapy remains a major public health problem. Recent studies show an alarmingly high rate of relapse after ECT despite conventional pharmacotherapy (C-PHARM). Continuation ECT (C-ECT) is also in widespread clinical use, however, its efficacy and safety have never been rigorously tested. The role of C-ECT in relapse prevention of seriously ill patients with MDD urgently needs to be defined. The ongoing study is a prospective, six-month, randomized clinical trial in which patients with MDD who remit with an acute course of bilateral ECT are randomized to one of two treatment arms: C-PHARM (nortriptyline + lithium) or C-ECT. The major hypothesis is that C-ECT will more effectively prevent relapse than C-PHARM. The two continuation therapies also will be compared in their effects on cognitive performance, global functioning, side effects, and perceived health status. Study design features include rigorous remitter criteria, blinded neuropsychological assessments, rigorous quality control procedures including independent, blind rating of videotaped Hamilton Depression Rating Scale and SCID interviews, and independent oversight of data collection and analysis. When completed, this project will provide the first and definitive data on the role of C-ECT in the treatment of serious affective illness.